Anti-fungal efficacy of combination of amphotericin B with colistin and gentamicin in McCarey-Kaufman corneal preservation medium

Purpose: To curtail the potential of donor corneal tissue disseminating fungi to the recipient抯 eye, we evaluated the addition of amphotericin B to McCarey?Kaufman (M?K)梒orneal storage medium supplemented with colistin. Methods: Amphotericin B was examined for its ability to inhibit the growth of Candida albicans and Aspergillus flavus using a microbroth dilution test and checkerboard assay in combination with only gentamicin and a combination of colistin, gentamicin, and amphotericin B. The safety on epithelium and endothelium was evaluated by 3?(4,5?dimethylthiazol?2?yl)?2, 5?diphenyltetrazolium bromide (MTT) assay. Results: The minimal inhibitory concentration of gentamicin was found to be >256 ?g/ml against both C. albicans and A. flavus, whereas that of amphotericin B was found to be in a range of 0.25�5 and 1�?g/ml for C. albicans and A. flavus, respectively. According to the checkerboard assay, 80% (4/5) of C. albicans isolates and 100% (5/5) of A. flavus isolates responded synergistically to the combination of amphotericin B and gentamicin, but only 20% (1/5) of C. albicans isolates showed an additive effect. None of the tested isolates displayed antagonism. The combined effect of the three drugs also did not display any antagonistic effect. Additionally, the MTT assay reveals no toxic effect of the antimicrobials used on corneal epithelial and endothelial cells. Conclusion: In vitro experiments demonstrate that amphotericin B is not toxic to either epithelium or endothelium and is a promising additive to the M?K medium supplemented with colistin.

Geotricosis: fungemia en paciente con leucemia linfoblástica aguda / Geotrichosis: fungemia in a patient with acute lymphoblastic leukemia

La fungemia por Geotrichum spp. es poco frecuente y altamente letal. En el Instituto Nacional de Cancerología de Bogotá solo se han reportado dos casos: uno entre el 2001 y el 2007, y el otro entre el 2012 y el 2018. Este tipo de infección es más común en pacientes con algún grado de compromiso del sistema inmunitario, por lo que puede presentarse en pacientes con neoplasias hematológicas malignas. Se presenta el caso de un hombre de 27 años con recaída de leucemia linfoblástica aguda, que ingresó con poliartralgias de cinco días de duración. También cursaba con neutropenia febril, celulitis sin abscesos y bacteriemia por Staphylococcus aureus resistente a la meticilina para lo cual recibió terapia con oxacilina y cefepime. Sin embargo, persistía la neutropenia febril por lo que se sospechó una infección fúngica invasora. Se tomó un nuevo set de hemocultivos y se inició tratamiento antifúngico. En los hemocultivos se identificaron artroconidias y mediante espectrometría de masas por láser de matriz asistida de ionización-desorción se confirmó la presencia de Geotrichum spp. Se ajustó el tratamiento antifúngico con deoxicolato de anfotericina B por 14 días y voriconazol por cuatro semanas. Luego de una estancia prolongada se le dio de alta. Aunque la incidencia de la fungemia por Geotrichum spp. es baja, en pacientes con neoplasias hematológicas malignas debe considerarse en el contexto de una neutropenia febril que es persistente a pesar del tratamiento antimicrobiano de amplio espectro. La identificación de los agentes causantes de fungemias con herramientas de proteómica, como la espectrometría de masas mencionada, permite ajustar el tratamiento dirigido y reducir las complicaciones, la estancia hospitalaria y la mortalidad.

Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, non- abscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.

Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura / Fusariosis in cancer patients: 13 case series report and literature review

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

Mucormycosis of left maxilla: A case report and review

Mucormycosis is an angioinvasive infection caused by fungi of the Zygomycetes order. Rhizopus is the main pathogen responsible for 90% of cases of cerebral mucormycosis. The term rhinocerebral mucormycosis should be used only in the face, palatal, orbital, paranasal sinus, or brain area. Here, we present the case of a 42-year-old man who presented with complaints of pain and swelling in relation to the left upper back tooth region for the past 20 days. In this case, the patient was immunocompromised due to type II diabetes, as well as COVID hospitalization. This case enlightens the investigation, as well as the management protocol followed by post-operative rehabilitation. Early diagnosis and prompt treatment can significantly reduce the morbidity and mortality of these deadly fungal infections.

Evaluation of liposomal amphotericin B for the treatment of fungal keratitis in a tertiary eye care hospital

Purpose: To evaluate the efficacy of liposomal amphotericin B (L?AMB) for the treatment of fungal keratitis. Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/ or confocal microscopy were administered topical L?AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months. Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P?value 0.04), and infiltrate size at presentation (P?value 0.04). At 3 months follow?up, no statistically significant difference was noted in BCVA and mean scar size among groups. Conclusion: L?AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance.

Uso de anfotericina B liposomal en leishmaniasis cutánea diseminada causada por Leishmania braziliensis en un paciente pediátrico con síndrome de Down / Use of liposomal anfotericin B in diseminated cutaneous leishmaniasis caused by Leishmania braziliensis in a pediatric patient with Down syndrome

Se presenta un caso de leishmaniasis selvática cutánea diseminada con manifestación extensa en una paciente pediátrica con síndrome de Down. El caso se confirmó a través de estudios parasitológicos e inmunológicos, mientras que la identificación se realizó mediante la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción (PCR-RFLP, por sus siglas en inglés), determinándose la especie como Leishmania (Viannia) braziliensis. La manifestación clínica agresiva y prolongada con poca respuesta a estibogluconato y anfotericina desoxicolato pueden deberse al déficit inmunológico que se presenta como parte del síndrome de Down. La paciente eventualmente recibió tratamiento con anfotericina B liposomal y al término de la terapia, mostró mejoría clínica de las lesiones. El presente reporte ilustra los desafíos tanto de diagnóstico como tratamiento de leishmaniasis cutánea en pacientes pediátricos inmunosuprimidos, especialmente en un entorno de difícil acceso social, económico y geográfico, a los servicios de salud. Se recomienda considerar a la leishmaniasis en el diagnóstico diferencial cuando se atienda ulceras crónicas dermatológicas atípicas; así como tener en cuenta el uso de anfotericina liposomal en pacientes inmunocomprometidos.

We present a case of disseminated cutaneous leishmaniasis with extensive manifestation in a pediatric patient with Down syndrome. The case was confirmed by parasitological and immunological tests. The species was identified as Leishmania (Viannia) braziliensis by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). The immune deficit that occurs as part of Down syndrome may have been the reason for the aggressive and prolonged clinical manifestations as well as the poor response to stibogluconate and deoxycholate amphotericin. The patient was treated with liposomal amphotericin B and at the end of therapy, showed clinical improvement of the lesions. This report highlights the challenges of the diagnosis and treatment of cutaneous leishmaniasis in immunosuppressed pediatric patients, especially under difficult social, economic and geographic conditions. Leishmaniasis should be considered as a differential diagnosis when treating atypical chronic dermatologic ulcers; the use of liposomal amphotericin in immunocompromised patients should also be considered in these cases.

Oxigenoterapia hiperbárica como tratamiento complementario en mucormicosis asociada a COVID-19: a propósito de dos casos / Hyperbaric oxygen therapy as an adjunctive treatment for COVID-19-associated mucormycosis: a report of two cases

Reportamos los dos primeros casos, en Perú, sobre el uso del tratamiento con oxigeno hiperbárico coadyuvante (TOHC) en pacientes con mucormicosis asociado a COVID-19 (MAC). El primer caso es una mujer de 41 años, con dolor en hemicara y región palatina izquierdas con rinorrea purulenta de un mes de evolución. Al examen físico, solo evidencia fístula oroantral. El segundo caso se trata de un varón de 35 años, con disminución de agudeza visual izquierda y dolor palatino con fístula que drena secreción purulenta de cuatro meses de evolución. Ambos pacientes tienen el antecedente de diabetes, tuvieron COVID-19 moderado cuatro meses antes del ingreso, y recibieron corticoterapia por este diagnóstico. Ambos pacientes tuvieron una evaluación tomográfica que mostró compromiso del seno maxilar y tejido óseo circundante, con endoscopia nasal diagnóstica y terapéutica para desbridamiento. Se obtuvieron muestras compatibles con mucormicosis en estudio histológico. Los pacientes fueron tratados con limpieza quirúrgica y anfotericina B desoxicolato, sin embargo, presentaron evoluciones tórpidas. Por lo tanto, se adicionó la TOHC y mostraron una mejoría evidente tras cuatro semanas de tratamiento con controles subsiguientes sin presencia de mucormicosis. Resaltamos la evolución de estos pacientes con TOHC, en una enfermedad con importante morbimortalidad, que ha sido emergente durante la pandemia.

We present the first two cases reported in Peru of the use of adjuvant hyperbaric oxygen therapy (HBOT) in patients with COVID-19-associated mucormycosis (CAM). The first case is a 41-year-old woman, with pain in the left side of the face and palatine region with purulent rhinorrhea for a month. Only an oroantral fistula was found during physical examination. The second case is a 35-year-old male, with decreased left visual acuity and palatal pain with a fistula, draining purulent secretion for four months. Both patients have history of diabetes, had moderate COVID-19 four months prior to admission, and received corticosteroid therapy for this diagnosis. Tomographic evaluation of both patients showed involvement of the maxillary sinus and surrounding bone tissue; both received diagnostic and therapeutic nasal endoscopy for debridement. Histological analysis showed that the samples were compatible with mucormycosis. The patients underwent debridement and were treated with amphotericin B deoxycholate; however, they presented torpid evolution. Then, HBOT was added and the patients showed an evident improvement after four weeks of treatment with subsequent controls without the presence of mucormycosis. We highlight the favorable evolution of these patients while receiving HBOT as treatment for a disease with high morbimortality, which emerged during the pandemic.

Disseminated mucormycosis in a child with acute lymphoblastic leukemia: autopsy findings / Mucormicosis diseminada en un paciente pediátrico con leucemia linfoblástica aguda: hallazgos de la autopsia

Abstract Background: Mucormycosis is a rare infection caused by ubiquitous fungi of the Mucorales order that mainly affects immunocompromised patients. These fungi have an important tropism for blood vessels that allows them to spread rapidly and cause thromboembolic events. Case report: We present a case of an 8-year-old male patient diagnosed with acute lymphoblastic leukemia treated with chemotherapy. He presented icteric syndrome, hepato-splenomegaly, and data of intestinal obstruction. Although he underwent intestinal resection, he did not improve and died. The autopsy identified disseminated mucormycosis involving the brain, lungs, esophagus, small intestine, colon, and pancreas. Conclusions: Hematological neoplastic diseases and their treatment are important risk factors for developing infections by opportunistic microorganisms such as mucormycosis. Early diagnosis and adequate treatment are essential due to their intrinsic difficulty and the high mortality rate of these cases.

Resumen Introducción: La mucormicosis es una infección poco frecuente causada por hongos ubicuos del orden de los Mucorales que afecta principalmente a pacientes inmunocomprometidos. Estos hongos poseen un importante tropismo por vasos sanguíneos que les permite diseminarse rápidamente y provocar lesiones trombo-embólicas. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 8 años con diagnóstico de leucemia linfoblástica aguda tratada con quimioterapia. Presentó síndrome ictérico, hepato-esplenomegalia y datos de obstrucción intestinal. A pesar de que fue sometido a resección intestinal, no presentó mejoría y falleció. En la autopsia se identificó mucormicosis diseminada con afección de cerebro, pulmones, esófago, intestino delgado, colon y páncreas. Conclusiones: Las enfermedades neoplásicas hematológicas y su tratamiento son importantes factores de riesgo para el desarrollo de infecciones por microorganismos oportunistas como la mucormicosis. El diagnóstico temprano y adecuado tratamiento son importantes debido a la dificultad intrínseca de los mismos y la alta tasa de mortalidad de estos casos.

Efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection：a meta-analysis / 中国药房

OBJECTIVE To compare efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， Wanfang， CNKI， CBM and VIP database， randomized controlled trial （RCT） and cohort study about 24 h continuous pump （trial group） versus intermittent infusion （control group） of amphotericin B were collected from the inception to Jan. 2023. After literature screening and data extraction， the quality of RCT was evaluated with modified Jadad scale， and the quality of cohort study was evaluated with Newcastle-Ottawa scale. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software. RESULTS A total of 7 literature were included， involving 1 RCT and 6 cohort studies with a total of 767 patients. The results of meta-analysis showed that the clinical effective rate [RR＝1.44， 95%CI （1.13，1.83）， P＝0.003] of trial group was significantly higher than that of control group， and all-cause mortality rate [RR＝0.37， 95%CI（0.19，0.72），P＝0.003] and the incidence rate of infusion reaction [RR＝0.28，95%CI（0.18，0.43）， P＜0.000 01] were significantly lower than control group； there was no statistical significance in the incidence rate of renal impairment between 2 groups [RR＝0.71，95%CI（0.45，1.11），P＝0.13] . The sensitivity analysis results showed that the results obtained in this study were robust. CONCLUSIONS The efficacy and safety of 24 h continuous pump of amphotericin B are better than those of intermittent infusion in the treatment of invasive fungal infection.

Analysis of risk factors for hypokalemia caused by amphotericin B liposome / 中国药房

OBJECTIVE To investigate the risk factors for hypokalemia caused by amphotericin B liposome， and to provide reference for clinical use of drugs. METHODS A retrospective analysis was used to collect the information of patients who used amphotericin B liposome during the hospitalization in First Affiliated Hospital of Hainan Medical College from January 2012 to December 2021. The details of use information about amphotericin B liposome and the potassium supplementation were collected. The patients were divided into hypokalemia group and normal group according to the occurrence of hypokalemia. Univariate and multi-variate Logistic regression analyses were used to analyze the risk factors for hypokalemia induced by amphotericin B liposome. RESULTS Of the 121 patients included in this analysis， 60 patients were in hypokalemia group， 61 patients were in normal group. The following parameters of the hypokalemic group were significantly higher or longer than those of the normal group， such as the maintenance dose， cumulative dose and maximum daily dose （in patients with severe hypokalemia） of amphotericin B liposome， treatment days， the maintained days of hypokalemia， daily dose of potassium supplement （in patients with moderate or severe hypokalemia）， the duration of potassium supplement （in patients with moderate hypokalemia）. Results of single factor analysis showed that the cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were independent risk factors of hypokalemia caused by this drug （P＜0.05）. Multi-variate analysis results showed that the presence of basic hypokalemia， body weight ＜50 kg， cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were the independent risk factors for hypokalemia caused by amphotericin B liposome （P＜0.05）. CONCLUSIONS The incidence of hypokalemia caused by amphotericin B liposome is high， the independent risk factors for hypokalemia include cumulative dose ≥200 mg， treatment days ≥5 days， the presence of basic hypokalemia and body weight ＜ 50 kg. It is suggested that serum potassium should be elevated to normal level before amphotericin B liposome treatment， and the level of serum potassium should be monitored during medication to reduce the occurrence of hypokalemia.

Central retinal vein occlusion as primary ocular manifestation of rhino-orbital-cerebral mucormycosis: A case report

Mucormycosis is a serious, rapidly progressing, life-threatening, and sight threatening fungal infection frequently seen in diabetics and immunocompromised patients. We report a rare occurrence of rhino-orbital mucormycosis presenting as unilateral central retinal vein occlusion (CRVO) and no other ocular signs of infection in a 65-year-old diabetic male. The definitive diagnosis was made by nasal biopsy which confirmed broad branching aseptate fungal hyphae. The patient was treated with amphotericin B for mucormycosis and intravitreal anti-vascular growth factor (anti-VEGF) drug for macular edema. To conclude, although ophthalmoplegia is the most common ocular presentation and retinal artery occlusion is the most common cause of visual loss in mucormycosis, it may have many varied presentations including CRVO. A high index of suspicion must be kept in diabetics and immunocompromised patients

Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India

Purpose: To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population. Methods: Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management. Results: Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3–16 ?g/mL, amphotericin B: 1–8 ?g/mL, voriconazole: 0.5–1.5 ?g/ mL, itraconazole: 0.5–12 ?g/mL, posaconazole: 0.094–1.5 ?g/mL. MIC against Aspergillus flavus was natamycin: 8–32 ?g/mL, amphotericin B: 0.5–16 ?g/mL, voriconazole: 0.025–4 ?g/mL, itraconazole: 0.125–8 ?g/mL, posaconazole: 0.047–0.25 ?g/mL; against Aspergillus niger isolates, to natamycin was 6 ?g/mL (n=1), amphotericin B 8–12 ?g/mL (n = 3), voriconazole: 0.125–0.19 ?g/mL (n = 3), itraconazole: 0.38–0.75 ?g/mL, posaconazole: 0.064–0.19 ?g/mL and against Aspergillus fumigatus (n = 1), was natamycin4 ?g/ mL, amphotericin B ? 8 ?g/mL, voriconazole 0.25 ?g/mL, itraconazole 1 ?g/mL, and posaconazole 0.19 ?g/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5–16 ?g/mL, amphotericin B: 0.5–8 ?g/mL, voriconazole: 0.19–3 ?g/mL, itraconazole: 0.125 ?g/mL, posaconazole: 0.125–0.5 ?g/mL and against susceptible Curvularia was natamycin 0.75–4 ?g/mL, amphotericin B 0.5–1 ?g/mL, voriconazole 0.125–0.19 ?g/mL, itraconazole 0.047–0.094 ?g/mL, posaconazole 0.047–0.094 ?g/mL. MIC against Mucor spp.+ Rhizopus spp. (n = 1) was natamycin: 8 ?g/mL, amphotericin B: 0.75 ?g/mL, posaconazole: 1.5 ?g/ mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 ?g/mL, posaconazole: 0.094 ?g/mL. MIC against Penicillium (n=1) was natamycin: 8 ?g/mL, voriconazole: 0.25 ?g/mL, itraconazole: 0.5 ?g/mL, and Posaconazole: 0.125 ?g/mL. Conclusion: Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates

COVID-19-associated Pulmonary Mucormycosis Study from a Tertiary Care Hospital, Rajkot, Gujarat, India: A Case Series

Background: The recent emergence of the coronavirus disease 2019 (COVID-19) had been associated with increased reporting of invasive mucormycosis, with high morbidity and mortality rates. According to Roden et al., pulmonary mucormycosis is the second most common presentation. Various risk factors associated with pulmonary mucormycosis besides COVID-19. The purpose of this study is to analyze patients\' demographic details, associated risk factors, and clinical and radiological findings and it confirms with histopathological examination for early diagnosis and management to improve outcomes. Materials and methods: This retrospective observational study was conducted on 16 patients with pulmonary mucormycosis confirmed with histopathology with a previous history of COVID-19 infection presenting to Pandit Dindayal Upadhyay Medical College Hospital, Rajkot, Gujarat, India, during the months of April朅ugust 2021. We evaluated the patients\' demographic details, clinical presentation, radiological findings, treatment, and outcomes. Results: We reported 16 cases with pulmonary mucormycosis; diagnosed after a mean of 36 days from the diagnosis of COVID-19. There was male predominance with a mean age of 54.5 years. Out of 16 patients, 14 (87.5%) survived, and 2 (12.5%) died during the course of treatment. The overall mortality rate was 12.5% in our study. Conclusion: The clinician should be aware of the possibility of pulmonary mucormycosis during and after the COVID-19 infection, especially in patients with underlying risk factors, and should enable early diagnosis and treatment to reduce morbidity and mortality to improve outcomes.

The impact of amphotericin B-fortified preservation media on donor rim cultures and posttransplant infection

Purpose: To determine the impact of amphotericin B supplementation to donor cornea preservation solutions on the rates of positive donor rim fungal cultures and postkeratoplasty fungal infections. Methods: This was a retrospective analysis of cases undergoing corneal transplantations at a single tertiary referral center from 2016 to 2021. Patients undergoing corneal transplantations with and without amphotericin B supplementation to the storage media were reviewed for donor rim culture results and postoperative infection. The primary outcome measures were positive donor rim fungal culture results and postkeratoplasty fungal infection. Results: A total of 1238 corneal transplants were analyzed. Of these, 849 were stored in preservation solution without amphotericin B, while 389 had amphotericin B included. There was a lower incidence of positive donor rim fungal cultures in cases with amphotericin B supplementation (1.8%) compared to the cases without amphotericin B (2.9%), although this difference was not statistically significant (P = 0.24). Of the 389 cases with amphotericin B supplementation, one (0.25%) went on to develop clinically significant infection, while three of 849 (0.35%) cases without amphotericin B developed infection. The sample size was too small to determine the effect of amphotericin B on the incidence of postkeratoplasty fungal infection. Conclusion: The addition of amphotericin B to donor cornea preservation solution resulted in a downward trend of positive donor rim fungal cultures and postkeratoplasty fungal infections, although these differences did not reach statistical significance. Further studies with larger sample sizes are necessary to appropriately determine the impact of amphotericin B supplementation in the storage solution on positive donor rims and postkeratoplasty fungal infections.

Leishmaniasis visceral con hemorragia masiva

RESUMEN Las complicaciones potencialmente mortales por el uso de la anfotericina B desoxicolato se presentan en menos del 1% de los casos. Entre ellas se describe el sangrado masivo principalmente por trombocitopenia. Se presenta caso de un paciente de sexo masculino de 38 años de edad, oriundo de una zona endémica, portador de leishmaniasis visceral grave que posterior al inicio de tratamiento con anfotericina B desoxicolato presenta hemorragia alveolar masiva por trombocitopenia.

ABSTRACT Life-threatening complications from the use of amphotericin B deoxycholate occur in less than 1% of cases. Among them, massive bleeding is described mainly due to thrombocytopenia. We present the case of a 38-year-old male patient, from an endemic area, with severe visceral leishmaniasis who, after starting treatment with amphotericin B deoxycholate, presented massive alveolar hemorrhage due to thrombocytopenia.

Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study

Background: Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited. Objectives: We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control. Methods: This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated. Results: Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed. Limitations: The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study. Conclusion: Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity

Resistant invasive Candida auris reported in neutropenic patients treated successfully with three antifungals

Candida auris is a deadly fungal pathogen able to cause fatal symptoms in immunocompromised patients. It may be misidentified and difficult to clinically diagnose. The guidelines are to employ Echinocandin and Amphotericin B in the treatment, but the following study elucidates successful treatment of infection by a combination of three classes of antifungal drugs; never reported before. We present a patient with fulminant acute disseminated encephalomyelitis and neutropenia who developed invasive candidiasis despite appropriate antifungal therapy. We successfully treated ongoing candidemia with three antifungal drugs which lead to the resolution of fungemia after 18 days of treatment. Isolation, segregation, waste disposal, and deep cleaning technique were also followed as recommended by the Infectious Diseases Society of America guidelines. First report ofCandidemia in an immunocompromised patient was successfully treated with three classes of antifungal drugs, IV Micafungin, Amphotericin B, and Posaconazole for nearly 18 days.

Rhino-orbito-cerebral mucormycosis caused by Rhizopus microsporus var. microsporus in a diabetic patient with COVID-19

Abstract COVID-19 disease caused by the SARS-CoV-2 coronavirus causes a wide range of clinical manifestations, ranging from mild to severe, with the main ones affecting the respiratory tract, such as pneumonia. In patients with greater severity, the high frequency of bacterial and fungal coinfection stands out, a situation related both to the patient's pre-existing comorbidities and due to the hospitalization itself. Cases of mucormycosis associated with COVID-19 were highlighted in the lay and scientific media, with the increase in mycosis cases being directly and indirectly attributed to the viral infection. This report describes a case of rhino-orbito-cerebral mucormycosis in a diabetic patient hospitalized for COVID-19, whose diagnosis was confirmed by identifying the agent Rhizopus microsporus var. microsporus through culture for fungi and PCR examination.

Adverse Drug Reactions to Antifungals Used in the Management of COVID-19 Associated Rhino-Orbito-Cerebral Mucormycosis

Objectives: To determine the incidence and frequency of adverse drug reactions (ADRs) to find out factors, if any contributing to the same, while also exploring the use of amphotericin B deoxycholate as a cheaper and safe alternative to liposomal amphotericin B. Materials and Methods: It was a cross-sectional observational study, with a study population of 50 conducted over three months after ethics approval. All adult patients admitted to a tertiary care center, in a metropolitan city of Maharashtra, diagnosed with Rhino-orbito-cerebral mucormycosis, with a history of previous COVID-19 infection and receiving antifungals for the treatment of the same were included in the study. Central Drugs Standard Control Organization (CDSCO) ADR reporting forms were used to collect data. Results: Electrolyte disturbances mainly hypokalemia were the most frequently encountered ADR with both Amphotericin formulations (39/50; 20.31%) followed by pain at the injection site (33/50; 17.19%). Nephrotoxicity occurred slightly more frequently with Amphotericin B Deoxycholate (19/29; 65%), compared to Liposomal Amphotericin B (11/19; 57%), while Posaconazole was mainly associated with gastrointestinal (GI) disturbances and hepatotoxicity. Conclusion: Amphotericin B Deoxycholate was associated most with ADRs, hypokalemia, and pain at the injection site being the most frequent. However, concerning nephrotoxicity, both Amphotericin formulations showed only a modest difference. Posaconazole was associated with the least number of ADRs and had a favorable safety profile.

Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India

Purpose: An unprecedented surge has been noted in rhino?orbital?Cerebral mucormycosis (ROCM) in times of current COVID?19 pandemic. The present prospective study aims to evaluate clinico?epidemiological profile, risk factors, management, and outcome of the cases of ROCM that presented to our tertiary care center during the study period from April to June 2021. Methods: All patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were staged and were treated with intravenous liposomal amphotericin B (AMB) and sino?nasal debridement of local necrotic tissue. Transcutaneous retrobulbar AMB (TRAMB), orbital decompression, and exenteration were instituted as indicated. All patients were followed up for a minimum of 6 months before arriving at the final outcome. Statistical analysis was performed. Results: A total of 49 patients presented during the study period, with a mean age of 42.2 years. The major risk factors included uncontrolled diabetes (89.8%), COVID?19 positivity (51.02%), and concurrent steroid use (38.77%). The most common presenting symptom was facial pain/swelling (43.65%), while the most common presenting sign was deterioration in vision (75.51%). Intravenous liposomal AMB was given to all patients along with sino?nasal debridement (85.71%), TRAMB (57.14%), orbital decompression (14.28%), and exenteration (12.24%). Overall, mortality at 6 months was 22.45% (11 patients). Age more than 60 years, intracranial extension, and HbA1c of more than 8.0% were observed to be statistically significant indicators of mortality. Conclusion: Early suspicion and timely diagnosis of mucormycosis at rhino?orbital stage is warranted in order to salvage life as well as visual function. TRAMB may prove as potentially favorable treatment modality in cases with limited orbital involvement.